tbuckley/cabot-search huggingface dataset:
Abstract 11032: Peptide Lv Promotes the Trafficking and Membrane Insertion of Endothelial K <sub>Ca</sub> 31 Through the MEK1/ERK Pathway
Authors: Dylan Pham, Autumn Niemi, Ria Blank, Gladys Ko
Journal: Circulation (2022)

Background: Peptide Lv is an endogenous secretory peptide that is upregulated in the eyes of patients with diabetic retinopathy, an ocular disease with pathological angiogenesis. Peptide Lv promotes vascular endothelial cell proliferation, migration, and sprouting, and blocking peptide Lv with a specific antibody, anti-Lv, dampens neovascularization, so peptide Lv is an angiogenic factor. However, the molecular mechanism of how peptide Lv promotes angiogenesis is not clear. We found that peptide Lv causes endothelial cell membrane hyperpolarization, a step that is essential in endothelium-dependent angiogenesis. Peptide Lv augments the protein expression and current densities of K Ca 3.1, an ion channel underlying the endothelial hyperpolarization. As ion channels require trafficking and insertion to the plasma membrane to be functional after they are expressed, we aimed to determine the downstream signaling of peptide Lv that is involved in the trafficking of K Ca 3.1 in endothelial cells. Hypothesis: Peptide Lv activates the MEK1/ERK signaling pathway to promote the trafficking and membrane insertion of K Ca 3.1 in endothelial cells. Blocking MEK1/ERK will prevent augmentation of K Ca 3.1 by peptide Lv. Methods: Cultured human umbilical vein endothelial cells (HUVECs) were treated with peptide Lv (500 ng/ml) or PBS (vehicle control) in the presence/absence of FR180402 (10 μM; an ERK inhibitor) or PD98059 (10 μM, a MEK1 inhibitor) followed by the patch-clamp electrophysiological recordings and biotinylation assays. Results: Blocking ERK activation attenuated the peptide Lv-meditated membrane hyperpolarization and increase of K Ca 3.1 currents in endothelial cells. Blocking ERK activation did not affect peptide Lv-elicited increases of K Ca 3.1 protein expression, but it reduced the level of membrane-bound K Ca 3.1 Conclusions: The MEK1/ERK signaling pathway mediates peptide Lv-elicited trafficking and membrane insertion of K Ca 3.1 but does not affect the increase of K Ca 3.1 expression by peptide Lv.
Abstract 10211: Cardiac MR Overlay Guides Endomyocardial Biopsy in Pediatric Transplant Patients Towards Regions of Interest
Authors: Michelle Udine, Devika P Richmann, Karin Hamann, Tacy E Downing, Joshua Kanter, Christopher Rossi, Steven Staffa, David Zurakowski, Russell Cross, Laura Olivieri
Journal: Circulation (2022)

Introduction: Endomyocardial biopsy (EMB) drives rejection diagnosis in pediatric heart transplant patients but is subject to false negatives. Cardiac magnetic resonance imaging (CMR) can detect and quantify fibrosis and edema with T1 and T2 mapping. Overlaying CMR data onto X-ray images may be used for EMB procedural guidance. Hypothesis: Overlaying segmented T1 and T2 map images onto X-ray for EMB guidance may improve diagnosis of rejection in pediatric transplant patients. Methods: 30 pediatric heart transplant patients referred for clinically indicated EMB underwent noncontrast CMR with T1 and T2 mapping prior to EMB. If present, regions of T1 and T2 elevation were segmented and exported as an overlay image. Biopsies were obtained without ( unguided ) and then with ( guided ) CMR overlay with T1 and T2 “hotspots”. Each biopsy specimen received a rejection grade, blinded to guided vs. unguided. As a surrogate for clinical rejection, treatment decisions were made without knowledge of CMR results, and logged as no change, oral therapy augmentation, or IV therapy initiation. Treatment category and pathologic grade were compared among biopsies with Fisher’s exact test and logistic regression. Results: 30 patients (median age 13 years (interquartile range (IQR) 8.8, 16.2), BSA 1.36 m2 (IQR 1.09, 1.86), 50% male) underwent 64 encounters for a total of 199 biopsied specimens (58 guided, 141 unguided). Hotspots were identified in 75% (48/64) of encounters, with 69% (33/48) in biopsied regions of the right ventricle allowing for guidance (25 T1 and 8 T2). Patients with T1 or T2 hotspots providing guided EMB were twice as likely to require any augmentation of therapy compared to those with unguided EMB (38% guided vs 17% unguided, p=0.001). Incidence of pathologic biopsy results (grade &gt; 0) was not significantly different between guided and unguided biopsies from the same patients (41% vs 40%, p =0.99). Conclusions: Patients with T1/T2 hotspots on CMR and guided EMB require rejection treatment more frequently than patients with only unguided biopsies, although biopsy grade did not significantly differ within the same patient. Future work will evaluate relationship of CMR T1 and T2 hotspots to treatment, which may establish CMR as a superior screening tool for rejection.
Abstract 10263: “High Blood Pressure Comes From Thinking Too Much”: Health Beliefs Among Couples With Cardiometabolic Disorders and HIV in Sub-Saharan Africa
Authors: Amy A Conroy, Julie T Bidwell, Allison Ruark, Rita Butterfield, Torsten Neilands, Sheri Weiser, Nancy Mulauzi, James Mkandawire, Jacqueline Huwa
Journal: Circulation (2022)

Introduction: People living with HIV are at increased risk for cardiometabolic disorders (CMD) due to chronic inflammation, immune activation, and antiretroviral therapy. In high HIV prevalence areas of sub-Saharan Africa, little is known about how HIV patients and their partners understand CMD and how health services could leverage partner support. Objective: To explore health beliefs among HIV patients with CMD and primary partners Methods: We conducted a qualitative study with 25 couples recruited from 3 HIV care clinics in Zomba, Malawi. Patients managing HIV and CMD (hypertension and/or diabetes) were enrolled first, followed by their primary partners. Semi-structured interviews were conducted separately with partners to elicit health beliefs around causality, prevention, and management of CMD. Dyadic data were coded for patterns and themes within couples and between couples, and data matrices were created to compare and contrast the findings. Results: Most participants believed that the main causes of CMD were diet, aging, and genetics, but some believed CMD was sexually transmitted or caused by viruses such as HIV. Within couples, diet and stress were the most commonly agreed-upon cause, and over half of couples believed “thinking too much” due to stress or couple conflict was a cause of CMD. Prevention beliefs included a healthy diet, exercise, avoiding HIV, using condoms, and keeping stress levels low. Management beliefs included dietary changes, taking medication or herbs, exercising, and reducing stress. Within couples, the most agreed-upon belief was that diet, particularly salt reduction, was important for prevention and management; however, within-dyad disagreement and incorrect beliefs around other aspects of a heart-healthy diet were common. Conclusion: While lifestyle factors were correctly identified as important for prevention and management of CMD, misconceptions remained around transmission through a virus or sex. Partners often differed in their views of CMD, which could interfere with CMD management. Health education programs are critically needed and involving partners may offer an opportunity to solidify knowledge in couples and foster collaborative disease management around CMD.
Abstract 10742: In-Hospital Virtual Peer-to-Peer Consultation to Improve Guideline-Directed Medical Therapy for Heart Failure: A Pilot Randomized Trial
Authors: Vishal N Rao, Anand Shah, Jaime McDermott, Stephanie Barnes, Evan Murray, Michelle D Kelsey, Stephen J Greene, Marat Fudim, Adam D Devore, Michael A BLAZING, Cara OBrien, Robert J Mentz
Journal: Circulation (2022)

Introduction: Guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) improves clinical outcomes and quality of life. Optimizing GDMT in the hospital is associated with greater long-term use in HFrEF. Hypothesis: A multidisciplinary virtual HF intervention improves GDMT optimization among patients with HFrEF admitted for any cause. Methods: In this pilot randomized, controlled study, consecutive patients with HFrEF admitted to non-cardiology medicine services for any cause were identified at Duke Hospital between May to September 2021. Major exclusions were end-stage renal disease, hemodynamic instability, and hospice care. Patients were randomized to a clinician-level virtual peer-to-peer consult intervention providing GDMT recommendations and information on medication costs vs. usual care. Primary endpoints included 1) proportion of patients with new GDMT initiation or use, and 2) changes to HF optimal medical therapy (OMT) scores which included target dosing (range 0-9). Results: Of 242 patients identified, 91 (38%) were eligible and randomized to intervention (N=52) or usual care (N=39). Baseline characteristics were similar between intervention and usual care (mean age 63 vs. 67 years, 23% vs. 26% female, 46% vs. 49% Black, mean EF 33% vs. 31%). GDMT use on admission was also similar. There were greater proportions of patients with GDMT initiation or continuation with the intervention compared with usual care ( Figure 1 ). After adjusting for OMT score on admission, changes to OMT score at discharge were higher for the intervention group compared with usual care (+0.44 vs. -0.31, absolute difference +0.75, adjusted estimate 0.86 ± 0.42; p=0.041). Conclusions: Among eligible patients with HFrEF hospitalized for any cause on non-cardiology services, a multidisciplinary pilot virtual HF consultation increased new GDMT initiation and dose optimization at discharge.
Abstract 10602: The Relationship Between Layered Plaque and Plaque Volume in Patients With Acute Coronary Syndromes
Authors: Haruhito Yuki, Akihiro Nakajima, Makoto Araki, Toru Naganuma, Lena Seegers, Daisuke Kinoshita, Keishi Suzuki, Iris McNulty, Hang Lee, Tsunekazu Kakuta, Sunao Nakamura, Ik-kyung Jang
Journal: Circulation (2022)

Introduction: Layered plaque is a signature of previous subclinical plaque destabilization and healing, which can be identified by optical coherence tomography (OCT). Silent plaque rupture or erosion with formation of a layer might contribute to rapid step-wise progression of plaque. We examined the relationship between layered plaques detected by OCT and plaque burden detected by intravascular ultrasound (IVUS) in patients with acute coronary syndromes (ACS). Methods: Patients presented with ACS who underwent preintervention OCT and IVUS were included in the analysis. Layered plaque was identified by OCT, and plaque burden was measured by IVUS around the culprit lesion. IVUS findings were compared between patients with layered plaque versus those without layered plaque. Results: Among 150 patients, total atheroma volume (TAV) (183.27 mm 3 [114.2 mm 3 to 275.0 mm 3 ] vs. 119.27 mm 3 [68.9 mm 3 to 185.5 mm 3 ], p=0.004), percent atheroma volume (PAV) (60.06 % [54.7 % to 60.1 %] vs. 53.69 % [46.8 % to 60.6 %], p=0.001), and plaque burden (PB) (86.51 % [81.7 % to 85.7 %] vs. 82.58 % [77.9 % to 85.4 %], p=0.001) were significantly higher in patients with layered plaques than non-layered plaques (Figure). When multi, single, and non-layered plaques were compared, TAV (188.69 mm 3 [122.1 mm 3 to 293.6 mm 3 ] vs. 137.85 mm 3 [100.1 mm 3 to 208.4 mm 3 ] vs. 119.27 mm 3 [68.9 mm 3 to 185.5 mm 3 ], p=0.021), PAV (62.12 % [56.8 % to 67.8 %] vs. 57.52 % [48.9 % to 60.1 %] vs. 53.69 % [46.8 % to 60.6 %] p&lt;0.001), and PB (87.44 % [81.8 % to 89.3 %] vs. 84.7 % [77.9 % to 88.0 %] vs. 82.58 % [77.9 % to 85.4 %], p=0.018) were significantly greater in multi-layered plaques than others. Conclusions: This study demonstrates that layered plaques, compared to non-layered plaques, have significantly greater plaque burden in patients with ACS, indicating plaque disruption and healing process, rather than gradual smooth muscle proliferation, significantly contributes to plaque progression at the culprit lesion in patients with ACS.
Abstract 10090: Computed Tomography is Non-Inferior to Cardiac Angiography in Differentiating Dual- versus Single- Supply Major Aortopulmonary Collaterals Among Patients With Pulmonary Atresia or Critical Stenosis
Authors: Khayri Shalhoub, Ashwin Prakash, Mohsin Ali, Kimberlee Gauvreau, Sunil J Ghelani, Nicola Maschietto
Journal: Circulation (2022)

Introduction: Anatomic characterization of pulmonary blood flow is of paramount importance in patients with major aortopulmonary collaterals (MAPCAs). Although computed tomography angiography (CTA) is an appealing alternative to cardiac angiography (CA), its ability to differentiate between single- versus dual-supply MAPCAs is not well-established. We investigated whether CTA is non-inferior to CA in defining MAPCAs supply. Methods: Retrospective analysis of patients who underwent both CTA and CA for MAPCA delineation between 2016-2021. Diagrams were created for patients labeling MAPCAs numerically for consistency in data collection. Images were independently reviewed by blinded CTA and CA readers. The diagnostic performance of CTA was compared to CA as the gold standard. Nonparametric paired tests were used for statistical analysis, and 95% confidence intervals were calculated using exact methods. Results: Seventeen patients, with 55 MAPCAs, met the study criteria. The median age at CTA and CA was 7 days (1-745) and 74 days (7-751), respectively. CA was performed under general anesthesia (GA) in all patients compared to 17% of CTAs (p=0.0001). Contrast load (median 2 vs 7.1 ml/kg) and adverse events (0 vs 47%) were lower in CTA than diagnostic CA (p &lt;0.0001 and p.=0.008, respectively). Fifty-three MAPCAs (96%) were concordantly classified as single or dual supply (95% CI, 87-100%). Compared to CA, CTA detected dual-supply MAPCAs with sensitivity of 97% (95% CI, 84-100%) and specificity of 96% (77-100%); similarly, PPV was 97% (84-100%) and NPV was 96% (77-100%). The proportion of MAPCAs labeled discordantly was non-inferior at both the 10% margin (p=0.0001) and 5% margin (p=0.031). Conclusions: CTA is accurate in differentiating single- versus dual-supply of MAPCAs. Additionally, CTA required a lower contrast load, less frequent use of GA, and resulted in fewer adverse events. Our results suggest that CTA may be used as the initial diagnostic modality for complete MAPCAs delineation, with CA reserved when an intervention or hemodynamic assessment is necessary.
Abstract 10395: Atherosclerotic Lesion in Chronic Thromboembolic Pulmonary Hypertension is Associated With Prolonged Symptom Duration
Authors: Jixiang Liu, Ziyi Chang, Zhu Zhang, Yishan Li, Kaiyuan Zhen, Han Tian, Wanmu Xie, Peiran B Yang, Zhenguo Zhai
Journal: Circulation (2022)

Background: The cause of atherosclerotic lesions in the pulmonary artery of patients with chronic thromboembolic pulmonary hypertension (CTEPH) remains unclear. We aimed to discuss the clinical characteristics of CTEPH patients with atherosclerotic lesions and further explore the unique metabolic pathway of atherosclerosis in the pulmonary artery. Methods: Following detailed pathological examination of the pulmonary endarterectomy (PEA) specimen, CTEPH patients were divided into two age- and sex-matched groups, those with and without atherosclerotic lesion (n=25 each), and their clinical characteristics were compared. Untargeted metabolomics were used to determine the different metabolites in the proximal lesions of the pulmonary artery. Results: 27.2% (25/92) of all PEA specimens were found with atherosclerotic lesions. Patients with atherosclerotic lesions were more likely to have a history of symptomatic embolism than those without atherosclerotic lesion (88% vs. 56%, P=0.012), including pulmonary embolism and deep venous thrombosis. Patients with atherosclerotic lesions were found to have longer symptom duration (8.0±6.5 vs. 4.7±4.2, P=0.039) and a lower rate of residual pulmonary hypertension after PEA than those without atherosclerotic lesion (40% vs. 56%). However, the existence of atherosclerotic lesion was not associated with pre-operative hemodynamic parameters and cardiac function. Metabolomic profiling revealed that the formation of atherosclerotic lesion in CTEPH is closely related to glycine, serine and threonine metabolic axes involved in cellular aging and energy metabolism. Conclusions: The occurrence of atherosclerotic lesions in the pulmonary artery of CTEPH was associated with symptomatic thromboembolic history and extended symptom duration. The results suggested a new link between atherosclerotic lesions and aberrant amino acid metabolism in the context of CTEPH. Further investigations focused on atherosclerotic lesion and pulmonary vascular remodeling may provide novel insight into the pathophysiology and new therapeutic strategies for CTEPH.
Abstract 107: Systemic Allogeneic Mesenchymal Stem Cell Administration Does Not Attenuate Early Post-resuscitation Brain Injury Or Inflammation In A Porcine Model Of Cardiac Arrest
Authors: Arezou Tajlil, Rosy Zel, Alexandra Wadhwani, Dorcas Nsumbu, Rebeccah Young, Brian R Weil
Journal: Circulation (2022)

Introduction: Based on emerging evidence that systemic inflammation exacerbates post-resuscitation organ injury, we recently tested the efficacy of allogeneic mesenchymal stem cell (MSC) administration early after return of spontaneous circulation (ROSC) in a porcine model of cardiac arrest (CA). Initial results indicate that MSCs attenuate post-ROSC cardiac dysfunction, but it is unclear if these protective effects extend to the brain. Accordingly, we aimed to determine if systemic allogeneic MSCs reduce early post-ROSC brain injury and inflammation in swine. Methods: Swine (n=33) were subjected to 10 min CA followed by mechanical CPR with defibrillation and epinephrine (EPI; 0.015 mg/kg iv). Animals that achieved ROSC (n=19) were blindly randomized to intra-arterial saline (n=9) or allogeneic bone marrow-derived MSCs (55±2 x 10 6 ; n=10) 30 min post-ROSC. Blood sampling was performed for 4 hours post-ROSC to quantify serum neurofilament light chain (NFL) levels, after which brain tissue was collected for post-mortem quantification of regional neuronal injury (H&amp;E), activated microglia (IBA-1), and inflammatory gene expression (PCR) vs. healthy control swine (n=8). Results: Animals resuscitated from CA exhibited a significant increase in neuronal injury throughout the brain vs. controls that was not affected by MSC treatment ( A ). Similarly, the post-ROSC rise in serum NFL was not different between saline-treated and MSC-treated animals (2.5±0.6 vs. 2.5±0.8 fold-change vs. baseline; p=0.94). A significant increase in activated microglia ( B ) and inflammatory gene expression ( C ) was observed throughout the brain in both CA groups vs. healthy controls, with particularly prominent changes in the striatum but no notable differences between treatment groups. Conclusions: Despite favorable effects on the heart, systemic allogeneic MSC therapy after ROSC does not significantly affect early markers of brain injury and inflammation in a porcine model of CA.
Abstract 10348: Contemporary Management of Cardiac Implantable Electronic Device Infection: A Survey of American College of Cardiology Members and Primary Care Physicians (COGNITO Study)
Authors: Ami Sood, Ulrika Birgersdotter-Green, Dhanunjaya Lakkireddy, Archana Rao, Paul Theriot
Journal: Circulation (2022)

Introduction: Cardiac implantable electronic devices (CIED) infection remains a serious complication associated with CIEDs. Complete extraction is a Class I recommendation for CIED infections, but a recent US Medicare analysis has demonstrated that there is a lack of guideline adherence with only 1 in 5 patients with a CIED infection undergoing extraction. Objective: To assess the current practice of US-based physicians related to the diagnosis and management of CIED infections and explore potential barriers to extraction. Methods: ACC performed a survey, based on a previous multinational EHRA/ESC needs assessment, to collect data from a mix of US physicians that may encounter CIED patients with complications. The survey timeframe was Feb 11 - Mar 10, 2022. Sampling techniques and screener questions were used to determine eligibility. The survey included questions based on knowledge and experience with CIED infection patients and multiple case scenarios. Results: The response rate was 20%, with a total of 387 physicians completing the survey. Less than half of clinicians polled (49%) indicated that they were familiar with the current HRS/AHA/EHRA/ESC guidelines regarding CIED infection. EPs (91%) were more familiar with these guidelines, compared to non-EP cardiologists (29%) and PCPs (23%). All EPs surveyed have had experience managing patients with CIEDs and nearly all (98%) have implanted these devices. Only two-thirds of non-EP cardiologists have experience with these patients. Only 30% of physicians specified that their institution had guideline-based protocols in place for managing patients with CIED infection. When presented with pocket infection cases, close to 50% of non-EP cardiologists and 70% of PCPs did not recommend guideline directed treatment. Conclusions: There are gaps in familiarity of guidelines as well as practical management of CIED infection with several non-extracting physician groups. Additionally, there is a lack of care pathways and other mechanisms in place for the management of CIED infection patients at most institutions. Addressing discrepancies, including guideline education and streamlining care/referral pathways, will be a key factor to bridging the gap and improving CIED infection patient outcomes.
Abstract 10298: Suboptimal Utilization of Validated Diagnostic Predictive Tools and D-Dimer in the Evaluation for Pulmonary Embolism in a New York City Public Hospital
Authors: Amrin Kharawala, Jiyoung Seo, Gabriel Hernandez Romero, Yunus Emre Demirhan, Manuel Hache-Marliere, Heitor Tavares Santos, Diego Barzallo, Charan Thej Reddy Vegivinti, Prasanth Balasubramanian, Gustavo J Duarte, Majd Al Deen Alhuarrat, Dimitrios Karamanis, Sanjana Nagraj, Dimitrios Varrias, Leonidas Palaiodimos
Journal: Circulation (2022)

Introduction: Computed tomography with pulmonary angiography (CTPA) is the gold standard for diagnosis of pulmonary embolism (PE). A nearly five-fold increase in the use of CTPA was observed from 2004 to 2016 in the United States. Hypothesis: Suboptimal utilization of validated diagnostic predictive tools with D-dimer might have led to excessive use of CTPA in a large public hospital in Bronx, New York. Methods: We conducted a retrospective review of patients who underwent CTPA from January to October 2021. Two independent reviewers, blinded to each other and to the CTPA and D-dimer results, estimated the clinical probability for PE using the Well’s criteria, YEARS criteria, and the revised Geneva score. Patients were classified based on the presence or absence of PE in the CTPA. Chi-square and Fischer's exact test were used to compare discrete variables. Results: 504 patients were included in the analysis (median age: 56 years, female: 59.1%). The clinical probability for PE was considered to be low by both independent reviewers in 303 (60.2%), 250 (49.7%), and 108 (21.5%) patients based on Well’s criteria, YEARS criteria, and the revised Geneva score, respectively. D-dimer testing was conducted in less than half of patients with low clinical probability [Well’s:(43.2%), YEARS:(49.7%), Geneva:(46.3%)]. Based on Well’s criteria, of 69/131 patients (52.7%) with a D-dimer &lt; 500 ng/ml, 3/69 (4.3%) were diagnosed with PE. As per YEARS criteria, of 51/100 patients (51%) with a D-dimer &lt; 500 ng/ml, 3/51 (5.9%) were diagnosed with PE. Based on the revised Geneva score, of 26/50 (52%) patients with a D-dimer of &lt; 500 ng/ml, 1/26 (3.8%) patient was diagnosed with PE. All PEs were subsegmental. Conclusion: Many patients underwent CTPA despite having a low probability of PE due to suboptimal utilization of validated diagnostic predictive tools with D-dimer. Using a D-dimer cut-off of &lt;500 ng/ml in patients with a low probability of PE would have missed only a small number of subsegmental PE.